dbSNP rs7350355: TMEM187:p.Met78Val (chrX-153982294-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003492.3(TMEM187):c.232A>G(p.Met78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,209,247 control chromosomes in the GnomAD database, including 35,343 homozygotes. There are 101,952 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 6339 hom., 12549 hem., cov: 25)

Exomes 𝑓: 0.24 ( 29004 hom. 89403 hem. )

Consequence

TMEM187
NM_003492.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

24 publications found

Variant links:

Genes affected

TMEM187 (HGNC:13705): (transmembrane protein 187) This gene consists of two exons and encodes a multi-pass membrane protein. An alternatively spliced transcript variant encoding the same protein has been found, but its biological validity is not determined. [provided by RefSeq, May 2010]

TMEM187 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.7919515E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM187	NM_003492.3 link	c.232A>G	p.Met78Val	missense_variant	Exon 2 of 2	ENST00000369982.5	NP_003483.1	Q14656

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TMEM187	ENST00000369982.5 link	c.232A>G	p.Met78Val	missense_variant	Exon 2 of 2	1	NM_003492.3	ENSP00000358999.4	Q14656
TMEM187	ENST00000425274.1 link	c.*34A>G		downstream_gene_variant		5		ENSP00000390108.1	C9JIP7
TMEM187	ENST00000431598.1 link	c.*133A>G		downstream_gene_variant		3		ENSP00000412872.1	C9JV55

Frequencies

GnomAD3 genomes

AF:

0.351

AC:

39582

AN:

112757

Hom.:

6330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.578

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.483

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.728

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.349

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.366

AC:

64874

AN:

177474

AF XY:

0.350

show subpopulations

Gnomad AFR exome

AF:

0.585

Gnomad AMR exome

AF:

0.618

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.725

Gnomad FIN exome

AF:

0.182

Gnomad NFE exome

AF:

0.175

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.238

AC:

260708

AN:

1096434

Hom.:

29004

Cov.:

AF XY:

0.247

AC XY:

89403

AN XY:

362302

show subpopulations

African (AFR)

AF:

0.582

AC:

15366

AN:

26389

American (AMR)

AF:

0.605

AC:

21162

AN:

35005

Ashkenazi Jewish (ASJ)

AF:

0.290

AC:

5614

AN:

19351

East Asian (EAS)

AF:

0.726

AC:

21890

AN:

30164

South Asian (SAS)

AF:

0.571

AC:

30897

AN:

54095

European-Finnish (FIN)

AF:

0.178

AC:

7073

AN:

39707

Middle Eastern (MID)

AF:

0.410

AC:

1659

AN:

4045

European-Non Finnish (NFE)

AF:

0.170

AC:

143337

AN:

841653

Other (OTH)

AF:

0.298

AC:

13710

AN:

46025

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

9256

18512

27769

37025

46281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5922

11844

17766

23688

29610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.351

AC:

39636

AN:

112813

Hom.:

6339

Cov.:

AF XY:

0.359

AC XY:

12549

AN XY:

35003

show subpopulations

African (AFR)

AF:

0.578

AC:

17965

AN:

31084

American (AMR)

AF:

0.484

AC:

5205

AN:

10756

Ashkenazi Jewish (ASJ)

AF:

0.263

AC:

698

AN:

2657

East Asian (EAS)

AF:

0.728

AC:

2602

AN:

3576

South Asian (SAS)

AF:

0.599

AC:

1698

AN:

2835

European-Finnish (FIN)

AF:

0.181

AC:

1132

AN:

6253

Middle Eastern (MID)

AF:

0.355

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.181

AC:

9619

AN:

53200

Other (OTH)

AF:

0.382

AC:

592

AN:

1551

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

768

1535

2303

3070

3838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.269

Hom.:

26168

Bravo

AF:

0.386

TwinsUK

AF:

0.175

AC:

648

ALSPAC

AF:

0.173

AC:

501

ESP6500AA

AF:

0.561

AC:

2148

ESP6500EA

AF:

0.183

AC:

1229

ExAC

AF:

0.351

AC:

42616

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-1.0

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.50

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.00072

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0000038

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

0.14

PrimateAI

Benign

0.43

PROVEAN

Benign

0.28

REVEL

Benign

0.029

Sift

Benign

0.32

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.012

MPC

0.16

ClinPred

0.0018

GERP RS

2.7

Varity_R

0.055

gMVP

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over